Sesquiterpene metabolites from Pogostemon cablin leaf essential oil as acetylcholinesterase inhibitors: An integrated computational and phytochemical study

IF 3.1 4区生物学 Q2 BIOLOGY

Computational Biology and Chemistry Pub Date : 2025-08-27 DOI:10.1016/j.compbiolchem.2025.108652

Prajisha Jayaprakash, Sujata Bhattacharyya, Handrika Saikia, Twahira Begum, Mohan Lal

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引用次数: 0

Abstract

Neurological disorders are the major factor of dementia worldwide, presenting significant and escalating challenges to global healthcare systems. Alzheimer's disease (AD) is a leading cause of dementia, creating substantial challenges for international healthcare. Medicinal and aromatic plants offer diverse pharmaceutical properties owing to their richness in chemical constituents. This study aimed to evaluate the in vitro anti-acetylcholinesterase activity of essential oil from Pogostemon cablin (patchouli), which demonstrated inhibitory potential, indicating its possible role in AD management. Preliminary phytochemical screening, followed by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, led to the identification of seventeen compounds, collectively accounting for 97.70 % of the total area, with patchouli alcohol (26.21 %) emerging as the predominant constituent. In-vitro anti-acetylcholinesterase activity tests revealed that sesquiterpene-rich patchouli essential oil had a lower (IC₅₀ 24.15 µg/mL) than the standard galantamine (IC₅₀ 25.66 µg/mL), highlighting the higher inhibition potential of patchouli essential oil on acetylcholinesterase. In-silico studies revealed that patchouli alcohol exhibited the highest binding affinity with a docking score of −8.5 kcal/mol, while 1H-Cycloprop[e]azulene, 1a,2,3,4,6,7,7a,7b-octahydro-1,1,4,7-tetramethyl showed the lowest docking score of −6.8 kcal/mol, highlighting the differential binding interactions of the compounds with the acetylcholinesterase enzyme. All key compounds demonstrated acceptable ADME properties, including compliance with Lipinski's rule of five, favorable topological polar surface area (TPSA), high gastrointestinal (GI) absorption, blood-brain barrier (BBB) permeability, and suitable bioavailability scores. Molecular dynamics simulations (600 ns) confirmed stable AChE-ligand interactions (six complexes), with RMSD values of ∼2.5–3.5 Å, SASA around 2050–2200 Å², and Rg between 21.8 and 23.4 Å, indicating compact and stable protein-ligand complexes, indicating its potential as an AD therapeutic agent.

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广藿香叶精油倍半萜代谢物作为乙酰胆碱酯酶抑制剂：综合计算和植物化学研究

神经系统疾病是全球范围内痴呆症的主要因素，对全球卫生保健系统提出了重大且不断升级的挑战。阿尔茨海默病（AD）是痴呆症的主要病因，给国际医疗保健带来了重大挑战。药用和芳香植物因其丰富的化学成分而具有多种药用特性。本研究旨在评价广藿香精油体外抗乙酰胆碱酯酶活性，发现广藿香精油具有抑制作用，提示其可能在AD治疗中起作用。初步的植物化学筛选，随后进行气相色谱-质谱（GC-MS）分析，鉴定出17种化合物，占总面积的97.70 %，其中广藿香醇（26.21 %）是主要成分。体外抗乙酰胆碱酯酶活性测试表明，富含倍半萜的广藿香精油的IC50（24.15 µg/mL）低于标准品加兰他明（25.66 µg/mL），表明广藿香精油对乙酰胆碱酯酶的抑制潜力更高。结果表明，广藿香醇具有最高的结合亲和力，对接得分为−8.5 kcal/mol，而1h -环丙[e]azulene， 1a,2,3,4,6,7,7a，7b-八氢-1,1,4,7-四甲基的对接得分最低，为−6.8 kcal/mol，突出了化合物与乙酰胆碱酯酶的不同结合作用。所有关键化合物均表现出可接受的ADME特性，包括符合Lipinski的五法则，良好的拓扑极性表面积（TPSA），高胃肠道（GI）吸收，血脑屏障（BBB）通透性和合适的生物利用度评分。分子动力学模拟（600 ns）证实了稳定的ache1 -配体相互作用（6个配合物），RMSD值为~ 2.5-3.5 Å， SASA约为2050-2200 Å²，Rg在21.8 - 23.4 Å之间，表明紧密而稳定的蛋白质-配体复合物，表明其作为AD治疗剂的潜力。

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来源期刊

Computational Biology and Chemistry 生物-计算机：跨学科应用

CiteScore

6.10

自引率

3.20%

发文量

142

审稿时长

24 days

期刊介绍： Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.